P680: SARCOPENIA EVALUATED BY CT SCAN IS ASSOCIATED WITH SHORTER SURVIVAL IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA TREATED WITH TARGETED THERAPIES. A PROSPECTIVE STUDY.
Authors: A. Visentin, F. Crimì, A. Corso, R. Angelone, C. A. Cavarretta, A. Cellini, F. Angotzi, V. Ruocco, S. Pravato, E. Quaia, L. Trentin
Journal: HemaSphere (2022)

Background: Chronic lymphocytic leukemia (CLL) usually affects elderly patients with comorbidities. Although drugs targeting BTK, BCL2 and PI3K have been proved to be better tolerated than chemoimmunotherapy and to improve the survival of CLL patients, comorbidities, assessed by Cumulative Illness Rating Scale (CIRS) score, are still associated with a worse outcome. Indexes of sarcopenia, subcutaneous or visceral adipose tissues assessed by CT scan, are emerging as survival markers in cancer patients. However, CT scan is not recommended by iwCLL guideline nor we known the clinical impact of body composition in CLL. Aims: The aim of this study was to assess the impact of muscle and adipose tissue indexes in patients with CLL treated with targeted agents. Methods: We performed a single center prospective study of CLL patients treated with BTK, BCL2 and PI3K inhibitors out of clinical trials. Inclusion criteria were diagnosis of CLL and need of treatment according to iwCLL guideline, creatinine clearance >30ml/min and CT scan performed at baseline. For each patient, with NIH ImageJ software, we extracted the areas of subcutaneous fat, visceral fat and the skeletal muscle from an unenhanced axial CT image at vertebra L3. The values obtained (cm2) were divided by the square of patient’s height (m2), obtaining the subcutaneous adipose tissue index (SATI), the visceral adipose tissue index (VATI) and the skeletal muscle index (SMI). Overall survival (OS) was calculated as months from starting targeted therapies to death (event) or last available follow-up (censored). Survival curves with Log-rank test. Results: We included 118 patients, 70 (59%) were males, mean age was 71.6±8.6 years, 74 (63%) were at Rai stage III-IV, 50 (42%) had a CIRS≥6, 96 (81%) unmutated IGHV, 41 (35%) 17p13 deletion, 39 (33%) TP53 mutation. The median number of therapies was 3 (range 1-9). Sixty-six patients (56%) received ibrutinib, 27 (23%) idelalisib+rituximab and 25 (21%) venetoclax±rituximab, including 17 (14%) front line therapies (13 ibrutinib, 4 venetoclax). We observed that SMI values correlated with SATI (p=0.035) and VATI (p<0.0001). SMI, SATI and VATI were higher in males vs females, median 48.4 vs 42.2 (p=0.007), 61.0 vs 67.9 (p=0.0087) and 70.0 vs 50.3 (p=0.0113)(Fig 1A). Using these thresholds, low-SMI, suggestive of sarcopenia, and low SATI correlated with a more advance number of previous therapies (p=0.027 and p=0,037). Low-SMI was more common in patients with CIRS≥6 (p=0.039). SMI, SATI and VATI did not correlated with age, stage and biological markers. After a median follow-up of 32 months the median OS for the whole cohort was 46.7 months. We confirmed that CIRS≥6 correlated with a worse OS in our study (p<0.0001, Fig. 1B). The 3-year OS was 53% and 66% for patients with low-SMI vs high-SMI, and the median OS was 40.3 months for low-SMI but not reached for high-SMI patients (p=0.0199, Fig. 1C). SATI and VATI did not correlate with OS. Combining data of CIRS≥6 and low-SMI, 40 (34%) patients, 47 (40%) and 31 (26%) displayed 0, 1 and 2 markers (Fig. 1D). The 3-year OS was 80%, 56% and 42% for patients at score 0, 1 and 2. The median OS was not reached for score 0 patients, but decreased from 42 to 23 months for patients at score 1 and 2 (p=0.0006, Fig. 1E). Image:Summary/Conclusion: In this prospective study we found that that basal CT scan identifies sarcopenic CLL patients with low SMI featured by an adverse prognosis even if treated with targeted oral drugs, in particular when combined with the CIRS score. The prognostic and predictive impact of basal CT scan in CLL deserves further investigation.